REPRESSION OF THROMBOSPONDIN-1 EXPRESSION, A NATURAL INHIBITOR OF ANGIOGENESIS, IN POLYOMA MIDDLE-T TRANSFORMED NIH3T3 CELLS

Thrombospondin-1 (TS1) is a modular extracellular matrix glycoprotein and expressed by many cell types in culture. Tnrombospondin-1 inhibits angiogenesis and its expression inversely correlates with the degree of invasiveness and metastasis in tumor cell lines. Here, we demonstra te that expression of Polyoma middle T oncogene in NIH3T3 cells result s not only in transformation but also represses expression of three th rombospondin isoforms, TS1, TS2, and TS3. Similar results were observe d in ras, and to a lesser extent in src transformed NIH3T3 cells. Midd le T and ras transformed cells expressed higher levels of c-jun mRNA, while the src transformed cells expressed higher levels of junB mRNA w hen compared to control cells. Thus, repression of thrombospondin leve ls appears to play an important role in establishment and maintenance of a malignant phenotype. This is mediated, at least in part, by alter ation in c-jun activity in middle T and ras transformed NIH3T3 cells.